Papers by Cristian Zenerino
Preeclampsia (PE) is a severe pregnancy-related syndrome characterized by exacerbated placental i... more Preeclampsia (PE) is a severe pregnancy-related syndrome characterized by exacerbated placental inflammation. LMWH has been used during PE since several trials described its anti-inflammatory effect. Nevertheless, LMWH mechanisms of action on the placental tissue are still unclear. HMGB1 is a transcription factor with an extracellular cytokine-like function that plays a pivotal role in the inflammatory process. HMGB1 bound to its receptor RAGE (Receptor for Advanced Glycation End products) is able to induce the transcription of the pro-inflammatory cytokine TNF-α and IL-6. LMWH binds to HMGB1 in-vitro, thus changing its structural conformation and inhibiting its activity. Since HMGB1 has been previously found up-regulated in PE, in the present study we investigated LMWH’s modulation of HMGB1/RAGE axis and its targets TNF-α and IL-6 in the placental tissues
Molecules (Basel, Switzerland), Jan 17, 2017
We evaluated whether physiological and pre-eclamptic (PE) placentae, characterized by exacerbated... more We evaluated whether physiological and pre-eclamptic (PE) placentae, characterized by exacerbated inflammation, presented alterations in pro-inflammatory High Mobility Group Box 1 (HMGB1) and its Receptor of Advanced Glycation End products (RAGE) expression. Moreover, we investigated, in physiological placental tissue, the ability of Low Molecular Weight Heparin (LMWH) to modify HMGB1 structural conformation thus inhibiting RAGE binding and HMGB1/RAGE axis inflammatory activity. HMGB1, RAGE, IL-6 and TNFα (HMGB1/RAGE targets) mRNA expression were assessed by Real Time PCR. HMGB1, RAGE protein levels were assessed by western blot assay. Physiological term placental explants were treated by 0.5 U LMWH for 24 or 48 h. HMGB1 and RAGE expression and association were evaluated in LMWH explants by RAGE immunoprecipitation followed by HMGB1 immunoblot. HMGB1 spatial localization was evaluated by immuofluorescent staining (IF). HMGB1 expression was increased in PE relative to physiological p...
Placenta, 2014
In the present study, we characterized the expression of Activating Protein 1 (AP-1) factors, key... more In the present study, we characterized the expression of Activating Protein 1 (AP-1) factors, key cell cycle regulators, in primary placental mesenchymal stromal cells (PDMSCs) derived from normal and preeclamptic (PE) pregnancies with fetal-placental compromise. Methods PDMSCs were isolated from control (n = 20) and preeclamptic (n = 24) placentae. AP-1 expression was determined by semi-quantitative RT-PCR (sqRT-PCR), Real Time PCR and Western Blot assay. PDMSCs were plated and JunB siRNA was performed. JunB and Cyclin-D1 expression were assessed by Real Time and Western Blot analyses. Results JunB expression was significantly increased while Cyclin-D1 expression was significantly downregulated in PE relative to control PDMSCs. JunB siRNA was accompanied by JunB downregulation and increased Cyclin-D1 in normal PDMSCs. Conclusions We described, for the first time, AP-1 expression in PDMSCs derived from physiological and PE placentae. Importantly, we demonstrated that JunB over-expression in PE-PDMSCs affects Cyclin-D1 regulation. Our data suggest a possible contribution of these pathological placental cells to the altered cell cycle regulation typical of preeclamptic placentae.
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Papers by Cristian Zenerino